(P-BT-22) Molecular Hemoglobinopathy Testing on Cord Blood Bank Samples

Inherited hemoglobin disorders (IHD) (sickle cell disorders and thalassemias) can be transmitted through hematopoietic stem cell transplantation. As Cord Blood (CB) banks become more diverse, prevalence of IHD might increase in the inventory. At our institution, HPLC screening is used at CB banking for all units to detect sickle cell disease and other structural variants. It is supplemented by molecular testing either to confirm ambiguous HPLC results or at the time of CB reservation in case of mean corpuscular volume (MCV) < 105fl (as a potential marker for a-thalassemia), family history of IHD or at transplant center’s (TC) request.

Study

Design/Methods:

At the time of collection, a complete blood count (CBC) is performed, with MCV. Maternal information regarding family history of IHD and race/ethnicity is obtained.

CB DNA samples are sent to the reference lab for molecular testing. The b-globin gene is analyzed by direct sequencing (to detect mutations); a-globin gene cluster is analyzed by deletion-specific PCR for the 7 most common deletions (- -^SEA/, - -^FIL/, - - ^THAI/, - -^MED/, - -^20.5/, -a^3.7/, -a^4.2/) and a^CS point mutation.

Results/Findings:

Between 1/1/2011 and 3/31/2023, 700 samples were sent for analysis (1.2% of overall inventory). CB were of White Non Hispanic (WNH) background for 119 (17%), from minorities (MN) for 559 (80%) and unknown for 22 (3%). IHD family history was present in 207 CB (30%).

Figure 1-A shows the repartition of testing reasons and positivity rates; 489 (70%) samples showed IHD (details in Figure 1-B).

IHD associated with no clinical signs and mild CBC anomalies (a-thalassemia silent carrier and silent b-globin mutations mainly) had, as expected, the lowest rate of positive family history (19 and 11%, respectively).

Combination of low MCV and family history had the highest rate of positivity (89%) (Figure 1-C). When MCV was low without family history, MN CB had the highest rate of positivity (77% vs 47% for WNH).

MCV was significantly lower with two a-globin gene deletions, as compared to one (Figure 1-C).

CB with homozygous defects or compound heterozygous were taken out of clinical inventory (n=18). The rest of the CB are available for clinical use, with IHD testing information added to the CB report.148 units with positive IHD were transplanted and no complaints were received.

Conclusions:

Molecular testing for IHD is a valuable tool for CB characterizations. Presence of IHD is an important information for transplant physician, as it can impact lab results post transplant. MCV, family history and donor race/ethnicity can be used to assess the type of IHD before results are available.